Even More Evidence That Ketamine Is an Antidepressant

According to a new analysis of people taking the hallucinogen for pain.

Doctors love ketamine, the hallucinogenic drug that can relieve pain at lower doses and function as anesthesia at higher ones. Ketamine can also help treat suicidal ideation, and some people are using it off-label for pain and treatment-resistant depression. It's an enticing medication as far as depression is concerned because it can start working in as little as 40 minutes, whereas traditional antidepressants can take weeks to kick in. But evidence of its antidepressant effects comes from anecdotes and studies involving fewer than 100 people—there has never been a large-scale clinical trial to test the safety and effectiveness of putting depressed people in a K-hole. Now a new analysis is offering more evidence that ketamine could help with depression.

For a paper in Scientific Reports, researchers at the Skaggs School of Pharmacy and Pharmaceutical Sciences at University of California San Diego dug into the Food and Drug Administration database where people report negative effects from medications; the FDA uses the Adverse Effect Reporting System (FAERS) to monitor for safety concerns. (The FDA approved ketamine as an anesthetic in 1970.)

But instead of looking for the negative things that people reported, the team was on the hunt for a lack of certain symptoms, specifically depression symptoms. The researchers found 41,000 submissions from people who received ketamine for pain between 2004 and 2016; they looked to see how many of those people reported depression symptoms.

Turns out that people who took ketamine for pain in addition to other pain drugs reported depression half as often as people taking any other painkillers or combination of pain drugs. People who got ketamine were also significantly less likely to say they had pain or experience opioid-associated side effects like constipation versus those taking other pain meds. The researchers also found antidepressant effects for three other drugs that aren't used for depression: the pain reliever diclofenac, the antibiotic minocycline, and Botox. (The team is now going to compare Botox to other cosmetic treatments like fillers to see if the effects observed were the result of improved self-image or the drug itself.)

It's possible that the pain-relieving properties of ketamine had something to do with the lower incidence of depression in this group (perhaps less pain equals less depression), but that's why the researchers compared ketamine-takers to people on other pain medications; it's the closest they could get to a control group. And the presence of this ketamine data in the FDA system means that people had some sort of adverse effect from it, and those included nausea, vomiting, and anxiety. Despite the side effects, the authors note that ketamine is effective enough that some insurance plans cover for depression if three other antidepressants fail.

This paper is a far cry from a clinical trial (since it was just data collected retrospectively) but the authors say that even having this data could help make the case for funding a clinical trial in the future. As senior author Ruben Abagyan, professor of pharmacy at UCSD, said in a release: "This study extends small-scale clinical evidence that ketamine can be used to alleviate depression, and provides needed solid statistical support for wider clinical applications and possibly larger scale clinical trials." A Johnson & Johnson subsidiary is already working on trials for treatment-resistant depression and depression with suicidal ideation.

The authors also noted that their data-mining method might uncover other benefits of drugs that have already been approved.